Unique tRNA Fragment Upregulation with SARS-CoV-2 but Not with SARS-CoV Infection
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Published:2023-12-28
Issue:1
Volume:25
Page:399
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Imirowicz Isabella1, Saifee Azeem1, Henry Leanne1, Tunkle Leo1, Popescu Alexander2ORCID, Huang Philip1ORCID, Jakpor Jibiana12, Barbano Ava12, Goru Rohit1, Gunawan Audrey1ORCID, Sicilia Maria2, Ono Mori1, Bao Xiaoyong3ORCID, Lee Inhan1
Affiliation:
1. Outreach Division, miRcore, Ann Arbor, MI 48104, USA 2. miRcore Volunteer Program, miRcore, Ann Arbor, MI 40104, USA 3. Department of Pediatrics, The University of Texas Medical Branch, Galveston, TX 77555, USA
Abstract
Unlike other coronaviruses, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly infected the global population, with some suffering long-term effects. Thanks to extensive data on SARS-CoV-2 made available through global, multi-level collaborative research, investigators are getting closer to understanding the mechanisms of SARS-CoV-2 infection. Here, using publicly available total and small RNAseq data of Calu3 cell lines, we conducted a comparative analysis of the changes in tRNA fragments (tRFs; regulatory small noncoding RNAs) in the context of severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 infections. We found extensive upregulation of multiple tRFs in SARS-CoV-2 infection that was not present in SARS-CoV or other virus infections our group has studied. By comparing the total RNA changes in matching samples, we identified significant downregulation of TRDMT1 (tRNA methyltransferase), only in SARS-CoV-2 infection, a potential upstream event. We further found enriched neural functions among downregulated genes with SARS-CoV-2 infection. Interestingly, theoretically predicted targets of the upregulated tRFs without considering mRNA expression data are also enriched in neural functions such as axon guidance. Based on a combination of expression data and theoretical calculations, we propose potential targets for tRFs. For example, among the mRNAs downregulated with SARS-CoV-2 infection (but not with SARS-CoV infection), SEMA3C is a theoretically calculated target of multiple upregulated tRFs and a ligand of NRP1, a SARS-CoV-2 receptor. Our analysis suggests that tRFs contribute to distinct neurological features seen in SARS-CoV-2.
Funder
NIH Research Pilot Grant from the Institute for Human Infections and Immunity (IHII) at UTMB
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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